1. Field of the Invention
The invention is directed to gene therapy and, more particularly, to the enhanced, non-viral delivery of genetic products to breast cancer cells.
2. Background Description
Current clinical therapeutic modalities for the treatment of breast cancer include chemotherapy and radiation treatment. These techniques effectively block the growth of breast cancer, and, in many cases, produce an apparent remission in this disease. However, there is often a recurrence of the disease, which may be a consequence of incomplete cell killing.
The reproductive hormone, estradiol, is typically found in the concentration range of 59-250 .mu.M in menstruating females. Estradiol is used in the treatment of various benign clinical disorders such as vasometer symptoms associated with menopause, atrophic vaginitis, osteoporosis, hypoestrogenism, and has also been utilized in the therapy of selected breast cancer patients. Pharmacological concentrations of estradiol used for treating breast cancer patients are known to produce growth inhibition and cell killing in experimental models of breast cancer. However, incomplete cell killing by estradiol together with reactivation of dormant cytostatic cells can lead to tumor recurrence
Viral gene delivery systems have been widely investigated. While these systems are relatively efficient, they are plagued by a number of problems including host toxicity, and immunogenic reactions. In addition, when viral carriers are used, there is the risk of delivering genomic mutations which can contribute to the reactivation of tumors and other maladies.
Recent clinical trials of non-viral, intra-tumor injection using lipid-based systems for gene-delivery have demonstrated that these methods are non-toxic and safe (see, Stewart et al., Human Gene Therapy, 3:267-275 (1992), and Hersh, Cancer Gene Therapy, Vol. 3, No. 6, 1996, p.S11). Lipofectamine.TM., a commercially available product available from Life Technologies of Gaithersburg, Md., is a lipid based liposome formulation which includes 3:1 w/w of the polycationic lipid 2,3-dioleyloxy-N-2(sperminecarboxamido)ethyl!-N,N-dimethyl-1-propanaminiu m trifluoroacetate (DOSPA) and the neutral lipid dioleoyl phosphatidylethanolamine (DOPE) in membrane filtered water. This product has been used for the transfection of DNA into cultured eukaryotic cells. Product literature indicates one milliliter is sufficient for 50-200 transfections on 35 mm tissue culture dishes or 15-70 transfections on 60 mm dishes. However, these methods have also proven to be relatively inefficient in that low levels of the delivered genes are expressed in few target cells.